Long-QT syndrome (LQTS) is an inherited (or in many cases drug-induced) cardiac rhythm disorder in which the QT interval on the surface electrocardiogram (EKG)—reflecting the time from initiation of ventricular depolarization to the end of ventricular repolarization—is prolonged. LQTS is associated with an increased propensity to syncope, polymorphous ventricular tachycardia, and sudden arrhythmic death. Two hereditary variants, the Romano-Ward syndrome and the extremely severe Jervell and Lange-Nielsen syndrome, which is associated with congenital deafness, have been comprehensively described since 1975.
LQTS is relatively infrequent with an estimated prevalence of 1 in 7,000 in the general population. LQTS causes 3,000-4,000 sudden deaths in children and young adults in the United States each year (NIH).
The voltage-gated potassium (Kv) channel KCNQ1 (Kv7.1) plays a major role in the electrophysiology of the heart where it is responsible for the formation of the slow-delayed rectifier current (IKS) – a critical component of repolarization of the cardiac action potential. Mutations identified in the genes encoding KCNQ1 account for approximately 50% of cases of LQTS, making inherited sequence variants the primary underlying cause of congenital long-QT syndrome – reflecting their essential role in ventricular repolarization.